Introduction: It is important to control both inflammation and immunosuppression after severe insults, such as sepsis, trauma, and surgery. Endotoxin tolerance is one of the immunosuppressive conditions and it has been known that endotoxin tolerance relates to poorer clinical outcomes in patients with severe insults. This study investigated whether whey protein hydrolysate (WPH) mitigates inflammation and endotoxin tolerance in THP-1 human monocytic leukemia cells.Methods: Endotoxin tolerance can be experimentally reproduced by two consecutive stimulations with lipopolysaccharide (LPS). THP-1 cells were incubated with LPS and WPH (first stimulation). After collecting the culture supernatant to evaluate the effect on inflammation, the cells were washed and restimulated by 100 ng/ml LPS (second stimulation). The culture supernatant was again collected to evaluate the effect on endotoxin tolerance. Concentrations of LPS and WPH in the first stimulation were adjusted to evaluate their dose dependency. Cytokine levels in the supernatant were determined by enzyme-linked immunosorbent assay. Statistical analysis was performed using the student's t-test or Dunnett's test.Results: Five mg/ml WPH significantly decreased interleukin (IL)-6 (p = .006) and IL-10 (p < .001) levels after the first LPS stimulation (1000 ng/ml). WPH significantly increased tumor necrosis factor-alpha (p < .001) and IL-10 (p = .014) levels after the second LPS stimulation. The suppressive effect of WPH on inflammation and endotoxin tolerance was dependent on the concentrations of LPS and WPH. The effective dose of WPH for endotoxin tolerance was lower than its effective dose for inflammation. Conclusion: WPH mitigated both inflammation and endotoxin tolerance.Therefore, WPH might be a candidate for valuable food ingredients to control both inflammation and immunosuppression after severe insults.

Intestinal barrier function declines with aging. We evaluated the effect of dietary fibers and indigestible oligosaccharides on intestinal barrier function by altering the microbiota of the elderly. The feces were anaerobically cultured with indigestible dextrin, inulin, partially hydrolyzed guar gum (PHGG), lactulose, raffinose, or alginate, and the fermented supernatant was added to inflammation-induced Caco-2/HT29-MTX-E12 co-cultured cells. Our data showed that inulin- and PHGG-derived supernatants exerted a protective effect on the intestinal barrier. The protective effect was significantly positively correlated with total short-chain fatty acids (SCFAs) and butyric acid production in the supernatant and negatively correlated with the claudin-2 (CLDN2) gene expression in the cultured cells. Furthermore, we showed that the CLDN2 levels are regulated by butyric acid. Thus, inulin and PHGG can change the intestinal environment of the elderly and maintain the intestinal barrier by accelerating the production of SCFAs and modifying the expression levels of barrier function-related genes.

BackgroundWhen exclusive breastfeeding is not possible, partially hydrolyzed formula (PHF) is often used as a starter formula for infants. Some children develop allergic symptoms, including anaphylaxis, after the first intake of cow protein. Therefore, the tolerability of PHF in infants with cow's milk allergy (CMA) is important information. Partially hydrolyzed whey formula (PHWF) is well characterized, but those containing both whey and casein are also available. We evaluated the characteristics of two whey and casein PHFs, PHF1 and PHF2, in vitro and ex vivo, and compared them with a PHWF, PHWF1.MethodsResidual antigenicity of β-lactoglobulin (β-LG) and casein in the formulas was measured using ELISA. The molecular weight profile was determined using high-pressure liquid chromatography. IgE reactivity and allergenic activity of the formulas were evaluated by ImmunoCAP inhibition assay and by basophil activation test using blood from patients with CMA, respectively.ResultsAll the participants (n = 10) had casein-specific IgE. The antigenicity of β-LG in PHF1 was similar to that in PHWF1, but it was slightly higher than that in PHWF1 for casein. PHF1 had a higher IgE reactivity than PHWF1. However, PHF1 and PHWF1 had a similar ability to activate basophils. PHF2 had lower antigenicity of casein and β-LG, IgE reactivity and basophil activation than PHWF1.ConclusionThese results suggest that the tolerability of PHF1 and PHF2 in patients with CMA is similar to and higher than that of PHWF1, respectively, and that the degree of IgE binding to PHFs does not necessarily correspond to basophil activation.

Objectives: The semi-elemental formula EDPAC-01 was administered to tube-fed patients in a clinical setting. Herein, this study aimed to evaluate its tolerability and efficacy. Methods: After a 2-week baseline period, the ongoing nutrition formula of tube-fed patients in long-term care was switched to EDPAC-01, which was administered for 4 weeks following the same energy intake. Tolerability was evaluated in terms of gastrointestinal symptoms, bowel movement, number of days with fever, adverse events, and side effects. Efficacy was evaluated in terms of body weight, serum albumin level, and transthyretin, formerly called prealbumin, level. An exploratory analysis on several laboratory test values was also performed. Results: The study included 13 participants. No serious severe adverse events were reported. The blood glucose level increased in one participant as a side effect, but was mild in severity and did not require treatment. No significant change was observed in any investigated measurement other than the transthyretin level. The transthyretin level was below the reference range in the baseline period (19.32 ± 5.53 mg/dL), but increased on week 2 of the feeding period (21.49 ± 5.88 mg/dL) and eventually reached the reference range by week 4 of the feeding period (22.74 ± 8.75 mg/dL). The exploratory analysis revealed a significant increase in total lymphocyte count and a significant decrease in urea nitrogen, triglyceride, and alkaline phosphatase levels. Conclusions: The semi-elemental formula EDPAC-01 is safe to use and potentially improves the nutritional status in tube-fed patients in long-term care.